Professional Documents
Culture Documents
673
June 2016
Draft document for comment
(June 2016)
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Should you have any comments on the attached text, please send these to
Dr S. Kopp, Group Lead, Medicines Quality Assurance, Technologies,
Standards and Norms (kopps@who.int) with a copy to Ms Marie Gaspard
(gaspardm@who.int) by 15 August 2016.
Medicines Quality Assurance working documents will be sent out
electronically only and will also be placed on the Medicines website for
comment under Current projects. If you do not already receive our
draft working documents please let us have your email address (to
bonnyw@who.int) and we will add it to our electronic mailing list.
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29 June
1 July 2015
Background information
The need for revision of the published Supplementary guidelines on good manufacturing
practices: validation (World Health Organization (WHO) Technical Report Series, No. 937,
2006, Annex 4) was identified by the Prequalification of Medicines Programme and a draft
document was circulated for comment in early 2013. The focus of the revision was the Appendix
on non-sterile process validation (Appendix 7), which had been revised and was adopted by the
Committee at its forty-ninth meeting in October 2014.
The main text was sent out for consultation as Working document QAS/15.639 entitled
Guidelines on Validation which constitute the general principles of the new guidance on
validation.
The draft on the specific topics, the appendices to this main text, will follow. One of them, i.e.
the Validation on qualification of systems, utilities and equipment, constitutes this working
document.
The following is an overview on the appendices that are intended to complement the general text
on validation:
Appendix 1
Validation of heating, ventilation and air-conditioning systems
will be replaced by cross-reference to WHO Guidelines on GMP for HVAC systems
for considerations in qualification of HVAC systems
(update - working document QAS/15.639/Rev.1)
Appendix 2
Validation of water systems for pharmaceutical use
will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical
use for consideration in qualification of water purification systems
Appendix 3
Cleaning validation consensus to retain
Appendix 4
Analytical method validation
will be replaced by update - working document QAS/16.671
Appendix 5
Validation of computerized systems
will be replaced by update - working document QAS/16.667
Appendix 6
Qualification of systems, utilities and equipment updated text proposed in this
working document
Appendix 7
Non-sterile process validation update already published as Annex 3, WHO Technical
Report Series, No. 992, 2015
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1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Principle
Scope
Glossary
General
User requirement specifications
Factory acceptance test and site acceptance test
Design qualication
Installation qualication
Operational qualication
Performance qualication
Requalication
Qualication of in use systems and equipment
1.
PRINCIPLE
1.1
Systems, utilities and equipment should be appropriately designed, located, installed,
operated, cleaned and maintained to suit their intended purpose.
1.2
Products should be manufactured on qualified equipment to ensure batch-to-batch
consistency
1.3
Procedures should be in place to ensure that systems, utilities and equipment remain in a
qualified state throughout the life of the system, utility and equipment.
2.
SCOPE
2.1
These guidelines describe the general aspects of qualication for systems, utilities and
equipment.
2.2
The principles in this guideline may also be applied to the qualification of instruments
and testing devices, where appropriate.
2.3
Systems, utilities and equipment that may have an impact on the quality of products,
should be appropriately qualied. These may include, where appropriate: computerized systems;
water purication systems; heating, ventilation and air conditioning systems; compressed air
systems; steam systems; production and quality control of equipment and instruments.
2.4
Documented impact assessments should support decisions for the exclusion of systems,
utilities and equipment from qualification.
3.
GLOSSARY
GENERAL
4.1
The validation master plan, or other relevant document, should specify the policy,
organization, planning, scope and stages applied in qualification for systems, utilities and
equipment and should cover, e.g. production, quality control and engineering.
4.2
The scope and extent of qualification and requalification should be determined based on
the principles of impact assessment and risk assessment. Risk management principles should be
considered in all areas of the scope and stages of qualification.
4.3
Where appropriate, new systems, utilities and equipment should pass through all stages of
qualication including the preparation of user requirement specifications (URS), design
qualication (DQ), installation qualication (IQ), operational qualication (OQ) and
performance qualication (PQ) (see Figure 1 as an example).
Figure 1. Examples of stages of qualification
PQ Test Plan
User Requirement
Specification
Performance
Qualification
Design
Qualification
(incl. UAT)
OQ Test Plan
Functional Design
Specification
Operational
Qualification
(incl. FAT)
DQ Test Plan
IQ Test Plan
(incl. PDI)
Installation
Qualification
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4.8
Qualication should be done in accordance with predetermined and approved
qualication protocols.
4.9
The results of the qualication should be recorded and reected in qualication reports.
4.10
4.11
4.12 Equipment should qualified and brought into routine use only once there is documented
evidence that it is t for its intended purpose.
4.13 Certain stages of the qualication may be done by the supplier or a third party, subject to
the conditions and responsibilities as defined in an agreement between the two parties. The
contract giver remains responsible to ensure that the qualification is done in accordance with
good manufacturing practices (GMP).
4.14 There should be a logical sequence in performing qualification. For example, operational
qualification should follow after the successful completion of installation qualification.
4.15 The relevant documentation associated with qualication including standard operating
procedures (SOPs), specications and acceptance criteria, certicates and manuals should be
maintained and be traceable.
4.16 Systems, utilities and equipment should be maintained in a qualified state and undergo
periodic requalication where appropriate, as well as requalication after change when needed.
4.17
5.
5.1
URS should be prepared for systems, utilities and equipment, where appropriate
5.2
URS should be used to verify, at a later stage, that the purchased and supplied system,
utility or equipment is in accordance with the manufacturers needs as specified.
6.
6.1
Where a system, utility or equipment is assembled, or partially assembled at a site other
than that of the purchaser or end-user, testing and verification should be done to ensure that the
system, utility or equipment is appropriate and ready for dispatch.
6.2
The checks and tests during assembly or partial assemble, should be recorded.
6.3
The acceptability of the assembly and overall status of the system, utility or equipment
should be described in a conclusion of the report for the factory acceptance test (FAT), prior to
shipment.
6.4
When the system, utility or equipment is received at the end user, tests should be
performed to verify the acceptability of the system, utility or equipment.
6.5
The results of the tests should be recorded and the outcome of the acceptability of the
system, utility or equipment recorded in the conclusion of the report for the site acceptance test
(SAT).
7.
DESIGN QUALIFICATION
7.1
URS should be considered when deciding on the specific design of a system, utility or
equipment.
7.2
A suitable supplier should be selected for the appropriate system, utility or equipment.
7.3
The supplier should be approved prior to purchasing the system, utility or equipment
7.4
On delivery of the system, utility or equipment, the user should verify that it meets the
agreed design specifications and satisfies the URS
7.5
8.
INSTALLATION QUALIFICATION
8.1
Systems, utilities and equipment should be correctly installed, in an appropriate location
and in accordance with an installation plan
8.2
There should be documented evidence of the installation. This should be in accordance
with the IQ protocol which contains all the required detail.
8.3
IQ should include identication and verication of all system elements, parts, services,
controls, gauges and other components.
8.4
Measuring, control and indicating devices being installed should be calibrated. The
calibration should be traceable to relevant national or international standards. Certificates should
be available.
8.5
8.6
The report should include at least the title, objective, site, details of the supplier and
manufacturer, system or equipment name and unique identification number, model and serial
number, date of installation, components and their identification numbers or codes, actual results
of tests and measurements, spare parts list, relevant procedures followed for tests and certicates
as applicable.
8.7
All deviations and non-conformances from URS, DQ and acceptance criteria specified,
observed during installation, should be recorded and investigated.
8.8
The outcome of the IQ should be recorded in the conclusion of the report, before OQ is
started.
8.9
Requirements and procedures for calibration, maintenance and cleaning should be drawn
up during installation.
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9.
OPERATIONAL QUALIFICATION
9.1
Systems, utilities and equipment should operate correctly and their operation should be
veried in accordance with an OQ protocol.
9.2
Critical operating parameters should be identied. Studies on the critical variables should
include conditions encompassing normal, upper and lower operating limits and circumstances
(this includes worst-case conditions).
9.3
OQ should include verication of operation of all system elements, parts, services,
controls, gauges and other components.
9.4
The results for the verification of operation should be documented in the OQ report to
indicate the satisfactory operation.
9.5
SOPs for the operation should be finalized and approved during this phase of
qualification.
9.6
Training of operators for the systems, utilities and equipment should be provided and
training records maintained.
9.7
Systems, utilities and equipment, as appropriate, should be released for PQ or routine use
after completion of OQ.
9.8
All calibration, cleaning, maintenance, training and related tests and results should be
verified to be acceptable. Any discrepancy or deviation should be recorded and investigated.
9.9
The outcome of the OQ should be recorded in the conclusion of the report, before PQ is
started.
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10.
PERFORMANCE QUALIFICATION
10.1 Systems, utilities and equipment should consistently perform in accordance with their
design specications. The performance should be veried in accordance with a PQ protocol.
10.2 There should be records for the PQ (report) to indicate the satisfactory performance over
a period of time. Manufacturers should justify the selected period over which PQ is done.
10.3
10.4 Where two stages of qualification (e.g. OQ and PQ) are performed simultaneously, or
where PQ is executed at the same time as process validation, appropriate justification for such a
decision should be documented
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11.
REQUALIFICATION
11.1 Systems, utilities and equipment should be maintained in a qualified state through the life
of the system, utility or equipment.
11.2 Routine requalication of systems, utilities and equipment should be considered based
on the outcome of risk management principles which include factors such as calibration,
verication and maintenance data and information.
11.3 The qualification status and requalification due dates should be documented in a dened
schedule.
11.4 The scope and extent of qualification should be determined based on risk assessment
when changes to an existing system, utility or equipment are made.
12.
12.1 There should be data to support and verify the suitable design, operation and performance
of systems, utilities and equipment that have been in use for a period of time and which have
not been subjected to IQ and or OQ.
12.2 In such cases, a qualification protocol and report should be prepared where elements of
design, operation and performance are verified for acceptability. These should include operating
parameters and limits for critical variables, calibration, maintenance and preventive maintenance,
SOPs and records.
***